The recent development of a structural parameterization of the energetics of protein folding has permitted the incorporation of the functions that describe the enthalpy, entropy, and heat capacity (i.e., the individual components of the Gibbs energy) into a statistical thermodynamic formalism that describes the distribution of conformational states under equilibrium conditions. The goal of this approach is to construct with the computer a large ensemble of conformational states, and then to derive the most probable population distribution (i.e., the distribution that best accounts for a wide array of experimental observables). This analysis has been applied to four different mutants of T4 lysozyme (S44A, S44G, V131A, V131G). It is shown that the structural parameterization predicts well the stability of the protein and the effects of the mutation. The entire set of folding constants per residue has been calculated for each mutant. In all cases the effect of the mutation propagates beyond the mutation site itself through sequence and three dimensional space. This effect occurrs despite the fact that the mutations are solvent-exposed sites and do not directly effect other interactions in the protein. These results suggest that single amino acid mutations at solvent exposed sites can be used to identify the extent of cooperative interactions in proteins. The magnitude and extent of these effects and the accuracy of the algorithm can be tested by means of NMR detected hydrogen exchange.